Emulsions permit extensive subdivision of an oil (using this term in a general sense) with a consequent formation of an enormous oil-water interface. Emulsions may be of the oil-in-water type or water-in-oil type and may involve other phases and interfaces. Where these dispersions are of the oil-in-water type, they are usually referred to as oil emulsions or soluble oil compositions. Where the phases are reversed as in a water-in-oil type, they are commonly referred to as inverted emulsions. There are many industrial uses of oil and water emulsions including paints, adhesives, lubricants, cleansing agents, soaps, insecticides, cosmetics, pharmaceuticals and therapeutic agents. This short list is only the beginning of a vast number of uses for oil and water emulsions.
One class of emulsions that has developed over a number of years is fluorocarbon emulsions as oxygen transport agents or artificial bloods. U.S. Pat. No. 3,911,138 which issued to Clark is an early example from the patent art which discloses perfluorocarbon emulsions as artificial bloods. As developed in this patent, neat fluorocarbon liquids cannot be injected into the blood stream, because their hydrophobic character makes them immiscible in the blood and, as a result, when they are transported in small blood vessels, they may cause vascular obstruction and death. As a consequence, for medical uses that require intravascular injection, highly fluorinated organic compounds or fluorochemicals must be dispersed as physiologically acceptable emulsions as developed in the above Clark patent and U.S. Pats. Nos. 4,110,474; 4,187,252 and 4,443,480.
There have been various attempts to make emulsions that are both stable and incorporate relatively large amounts of fluorocarbons that are required in clinical practice where the total volume of the emulsion that can be administered is limited, e.g., as in artificial bloods. An objective in the preparation of such emulsions is the employment of an acceptable fluorocarbon that may be excreted from the body within a clinically acceptable time period. Furthermore, compositions are required that are sterilizable without destruction of their stability.
A fluorocarbon emulsion that has been approved by the FDA is FLUOSOL DA which is an emulsion of perfluorodecalin and perfluorotripropylamine in a mixture of two surfactants, namely, egg yolk phospholipid and Pluronic F-68. This product, however, is not stable in the liquid state and must be stored frozen. Furthermore, the required presence of the perfluorotripropylamine in this emulsion to help stabilize it disadvantages the emulsion's medical usefulness because the half life of the perfluorotripropylamine in the liver and other body tissues is longer than desirable (see K. Yokoyama et al, "A Perfluorochemical Emulsion as an Oxygen Carrier" Artif. Organs (Cleve), 8 (1) pp. 34-40 (1984)). Finally, this emulsion contains only about 12% fluorocarbon by volume and thus it is much less therapeutically effective than desired because of its low oxygen content capacity.
Various surfactants have also been investigated in an attempt to produce useful and stable emulsions of fluorocarbons as oxygen transport agents in artificial bloods. For example, fluorocarbon emulsions containing a hydrogenated phospholipid, a nonionic polymeric surfactant and a surfactant selected from C6-22 fatty acids, their salts and monoglycerides, must also be stored at 4.degree. C. See, e.g., Japanese Pat. Appln. 59-067,229; U.S. Pat. No. 4,252,827 and German Offen. DE 2630506.
European Pat. Appln. 87300454.3 of Clark and Shaw describes novel emulsions of highly fluorinated organic compounds for use as oxygen transport agents and artificial bloods. This Clark and Shaw application discloses emulsions that are stable even when they contain higher levels of perfluorocarbons of up to about 75% by volume. The fluorocarbons of these emulsions display acceptable rapid excretion times from the liver and other body tissues, as well as being easily sterilized. These emulsions contain an oil as an emulsifying adjuvant in a composition containing the fluorochemical, surfactant and water. While improvements disclosed in this Clark and Shaw application are significant and alleviate many of the difficulties in the long search for effective transport agents in artificial bloods, there is a continuing need for further development.
In brief, emulsions of the oil and water type provide a very important role in many industries and numerous patents have been granted covering them. Research continues with efforts toward developing new emulsifying agents that provide emulsions having greater stability and broader utility in many industries including medical and non-medical fields.